Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


The Effect on MTX Polyglutamate Concentration Profile after Changing from Oral to Subcutaneous Methotrexate in Rheumatoid Arthritis.

Stamp4,  Lisa K., O'Donnell1,  John L., Chapman3,  Peter, Zhang2,  Mei, James3,  Jill, Frampton5,  Christopher, Barclay5,  Murray

Canterbury Health Laboratories, Christchurch, New Zealand
Canterbury Health Laboratories
Christchurch Hospital
University of Otago, Christchurch, New Zealand
University of Otago

Background:

The pharmacokinetics of oral methotrexate (MTX) in RA have been described previously (1). Some patients may change from the oral to subcutaneous (SC) route of administration to try to reduce adverse effects or improve disease control. The aim of this study was to determine the effect of changing from oral to SC administration of MTX on the concentrations of red blood cell MTX polyglutamates (RBC MTXGlun).

Methods:

Twenty-two patients on stable dose weekly oral MTX were changed to SC weekly MTX at the same dose. Trough RBC MTXGlun concentrations were measured by HPLC in samples taken weekly until week 8, then fortnightly until week 16 and then 4-weekly until week 24. Median concentrations were fitted to a standard first-order exponential model with Graph Pad Prism 5.0.

Results:

Of the 22 patients, 72.7% were female and mean age was 53.4 years (32–70). The mean duration of RA was 7.3 years (0.75 – 21). All patients were receiving 20mg MTX weekly followed by folic acid 5mg/week four days later. There were no dose changes during the study period.

RBC MTXGlu3, MTXGlu4, and MTXGlu5 concentrations increased significantly from week 0 to week 24, by factors of 1.3, 1.9 and 2.6-fold respectively. However, there was no significant change in RBC MTXGlu1 or MTXGlu2 concentrations. There was a significant reduction in the proportion of RBC MTXGlu1 and MTXGlu2 and increase in the proportions of RBC MTXGlu3, MTXGlu4, MTXGlu5 and MTXGlu3–5 contributing to the total RBC MTXGlu from week 0 to week 24.

MTXGlu3, MTXGlu4, MTXGlu5 and MTXGlu3–5 concentrations fitted the first-order exponential model well whilst MTXGlu1 and MTXGlu2 fitted poorly (Figure). The half-life of accumulation was 8.9 weeks for MTXGlu3, 12.2 weeks for MTXGlu4 and 9.9 weeks for MTXGlu5 and 10.4 weeks for MTXGlu3–5. The time to achieve 90% of steady state was 29.8 weeks for MTXGlu3, 40.4 weeks for MTXGlu4 and 33.2 weeks for MTXGlu5 and 34.5 weeks for MTXGlu3–5.

Conclusions:

Changing from oral to SC MTX resulted in an alteration in the ratio of short and long chain MTX polyglutamates. It took at least 6 months for long chain MTX polyglutamates to reach 90% of steady state after changing to SC administration. However, the time to reach steady state was shorter than that observed in patients commencing oral MTX. Adequate time must be allowed to determine clinical response to a change in route of administration of MTX.

Figure 1. Median MTXGlun concentrations and fitted curves over 24 weeks.

Reference:

1.Dalrymple, JM, Stamp, LK, O'Donnell, JL, Chapman, PT, Zhang, M & Barclay, ML. Pharmacokinetics of Oral Methotrexate in Patients with Rheumatoid Arthritis. Arthritis Rheum 2008;58:3299-308.

To cite this abstract, please use the following information:
Stamp, Lisa K., O'Donnell, John L., Chapman, Peter, Zhang, Mei, James, Jill, Frampton, Christopher, et al; The Effect on MTX Polyglutamate Concentration Profile after Changing from Oral to Subcutaneous Methotrexate in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :417
DOI: 10.1002/art.28186

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